Oxidative Stress and Microglial Cells in Parkinson's Disease

Figure 1

Canonical and noncanonical pathways of NF-κB activation. Proinflammatory activation signals such as LPS or TNFα activate the canonical pathway through the activation of the IKK complex, which includes the subunits IKKγ (NF-κB essential modulator, or NEMO), IKKα, and IKKβ. This complex then phosphorylates IkBα (the NF-κB inhibitor), which causes it to be ubiquitinated and proteolytically cleaved by the proteosome, releasing the p50/p65 heterodimer to be translocated to the nucleus, where it transcriptionally activates proinflammatory genes, including p47 and p67 of the NADPH oxidase complex. Growth and differentiation signals such as BAFF and CD40L activate the noncanonical pathway, which is initiated by NF-κB inducing kinase (NIK), which phosphorylates the IKKα homidimer complex which does not require either IKKγ or IKKβ, which subsequently phosphorylates the p100 subunit of the p100/RelB complex. The p100 protein is cleaved, which allows the p52/RelB complex to translocate to the nucleus and activate a number of growth and survival genes in target cells.